Canonical and atypical E2Fs regulate the mammalian endocycle

Hui Zi Chen, Madhu M. Ouseph, Jing Li, Thierry Pécot, Veda Chokshi, Lindsey Kent, Sooin Bae, Morgan Byrne, Camille Duran, Grant Comstock, Prashant Trikha, Markus Mair, Shantibhusan Senapati, Chelsea K. Martin, Sagar Gandhi, Nicholas Wilson, Bin Liu, Yi Wen Huang, John C. Thompson, Sundaresan RamanShantanu Singh, Marcelo Leone, Raghu Machiraju, Kun Huang, Xiaokui Mo, Soledad Fernandez, Ilona Kalaszczynska, Debra J. Wolgemuth, Piotr Sicinski, Tim Huang, Victor Jin, Gustavo Leone

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals.

Original languageEnglish (US)
Pages (from-to)1192-1202
Number of pages11
JournalNature Cell Biology
Issue number11
StatePublished - Nov 2012
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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